Variant 11-16789264-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001329630.2(PLEKHA7):c.3189A>C(p.Ser1063=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,613,628 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00095 ( 3 hom., cov: 33)

Exomes 𝑓: 0.000099 ( 0 hom. )

Consequence

PLEKHA7
NM_001329630.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.222

Variant links:

Genes affected

PLEKHA7 (HGNC:27049): (pleckstrin homology domain containing A7) Enables delta-catenin binding activity. Involved in epithelial cell-cell adhesion; pore complex assembly; and zonula adherens maintenance. Located in several cellular components, including centrosome; nucleoplasm; and zonula adherens. Part of pore complex. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHA7 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013082981).

BP6

Variant 11-16789264-T-G is Benign according to our data. Variant chr11-16789264-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3037586.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.222 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLEKHA7	NM_001329630.2 linkuse as main transcript	c.3189A>C	p.Ser1063=	synonymous_variant	23/27	ENST00000531066.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLEKHA7	ENST00000531066.6 linkuse as main transcript	c.3189A>C	p.Ser1063=	synonymous_variant	23/27	5	NM_001329630.2	A1

Frequencies

GnomAD3 genomes

AF:

0.000946

AC:

144

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00297

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.000253

AC:

AN:

248628

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

134642

show subpopulations

Gnomad AFR exome

AF:

0.00351

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000985

AC:

144

AN:

1461344

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

727004

show subpopulations

Gnomad4 AFR exome

AF:

0.00332

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.000248

GnomAD4 genome

AF:

0.000946

AC:

144

AN:

152284

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00296

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000585

Hom.:

Bravo

AF:

0.00106

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000280

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PLEKHA7-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 02, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.9

DANN

Benign

0.91

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.61

M_CAP

Benign

0.0034

MetaRNN

Benign

0.013

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

D;D;D;N

PROVEAN

Pathogenic

-6.0

REVEL

Uncertain

0.54

Vest4

0.27

MVP

0.25

ClinPred

0.070

GERP RS

-1.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over